Rapid and sustained improvements in health-related quality of life, fatigue, and other patient-reported outcomes in rheumatoid arthritis patients treated with certolizumab pegol plus methotrexate over 1 year: results from the RAPID 1 randomized controlled trial

Abstract Introduction The objective of this study was to assess the impact of certolizumab pegol (CZP) treatment on health-related quality of life (HRQoL), fatigue and other patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA). Methods Patients with active RA (N = 982) were randomized 2:2:1 to subcutaneous CZP (400 mg at weeks 0, 2 and 4; followed by CZP 200 mg or 400 mg) plus methotrexate (MTX) every other week, or placebo (PBO) plus MTX. PRO assessments included HRQoL, fatigue, physical function, arthritis pain and disease activity. Adjusted mean changes from baseline in all PROs were obtained using analysis of covariance (ANCOVA) applying last observation carried forward (LOCF) imputation. The proportion of patients achieving clinically meaningful improvements in each PRO was obtained using logistic regression and by applying non-responder imputation to missing values after rescue medication or withdrawal. The correlations between PRO responses and clinical responses were also assessed by tetrachoric correlation using non-responder imputation. Results Patients treated with CZP plus MTX reported significant (P < 0.001), clinically meaningful improvements in HRQoL at the first assessment (week 12); reductions in fatigue, disease activity and pain and improvements in physical function were reported at week 1. In particular, CZP-treated patients reported improvements in mental health. Mean changes from baseline in the SF-36 Mental Component Summary (MCS) at week 52 for CZP 200 mg and 400 mg plus MTX, and PBO plus MTX were 6.4, 6.4 and 2.1, respectively (P < 0.001). In addition, mental health and vitality scores in CZP-treated patients approached age- and gender-adjusted US population norms. Improvements in all PROs were sustained. Similar benefits were reported with both CZP doses. Changes in SF-36 MCS scores had the lowest correlation with disease activity scores (DAS28) and American College of Rheumatology 20% improvement (ACR20) response rates, while improvements in pain showed the highest correlation. Conclusions Treatment with CZP plus MTX resulted in rapid and sustained improvements in all PROs, indicating that the benefits of CZP extend beyond clinical efficacy endpoints into areas that are more relevant and meaningful for patients on a daily basis. Trial Registration ClinicalTrials.gov NCT00152386

L'immunité cellulaire d'Asterias rubens L. (Echinodermata) :caractérisation et impact de contaminations métalliques

Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

L'immunité cellulaire d'Asterias rubens L. (Echinodermata) :caractérisation et impact de contaminations métalliques

Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

Interaction of metals with peroxidase-mediated luminol-enhanced chemiluminescence (PLmCL)

The peroxidase-mediated luminol-enhanced chemiluminescence (PLmCL) method has been used to study the in vitro effect of contaminants such as heavy metals on the reactive oxygen species production by immunocytes. We were interested to know whether metals could directly affect peroxidase-mediated luminescence, taking horseradish peroxidase (HRP) as a model enzyme, since this could contribute to the inhibition of immunocyte LmCL. Copper inhibited PLmCL in a dose-dependent manner, while cadmium, iron, silver and lead only partly decreased the signal in the concentration range tested. In contrast, zinc enhanced the signal at high concentrations. Eventually, chromium, mercury and aluminium did not affect PLmCL. It is suggested that these effects reflect the ability of the metals to interact with the active site of the peroxidase. These results demonstrate that such interactions have to be considered when interpreting the effects of metals on immunocytes using the LmCL method. Copyright © 2004 John Wiley & Sons, Ltd.IF: 1,297info:eu-repo/semantics/publishe

Echinoderm reactive oxygen species (ROS) production measured by peroxidase, luminol-enhanced chemiluminescence (PLCL) as an immunotoxicological tool

info:eu-repo/semantics/publishe

Environmental factors influencing the immune responses of the common European starfish (Asterias rubens)

The influence of handling, salinity, temperature, parasitism, and gender on the immune responses (reactive oxygen species (ROS) production and coelomic amoebocyte concentration (CAC) of the starfish Asterias rubens was investigated in experimental conditions. Additionally, a year-round monthly survey in two distant sites was conducted in order to understand which of these factors most influences the immunity of A. rubens in field conditions. All considered factors, except gender and handling stress, influenced the studied immune responses of A. rubens in experimental conditions. Amoebocyte ROS production was increased at low salinity and at the lowest temperature tested (6°C). Amoebocyte concentration in the coelomic fluid was increased in starfish infested by the ciliate Orchitophrya stellarum. However, among all these factors, only temperature could be linked with the variability in ROS production measured in the field during the monthly survey. The variability in amoebocyte concentration in the field does not seem to be linked to any of the factors considered in this study; it appears to reflect mostly an inter-individual variation rather than seasonal fluctuations. Recommended periods and indicative values of immune responses are proposed for field studies using A. rubens. © 2003 Elsevier Ltd. All rights reserved.IF:1,851info:eu-repo/semantics/publishe